METHOD FOR SCREENING INHIBITORS TARGETING ANTI-APOPTOTIC SURVIVAL PATHWAYS

摘要

A method of identifying inhibitors of the anti-apoptotic survival pathway in cancer cells is disclosed. The method comprises the steps of (a) exposing cultured wild-type cells to a candidate inhibitor at a predetermined concentration for a predetermined period of time and determining cell viability after the exposure to the candidate inhibitor; (b) exposing two or more cell lines of specifically MCL-1 or BCL-2 or BCL-X_L addicted cells to the candidate inhibitor at the predetermined concentration for the predetermined period of time and determining cell viability after the exposure to the candidate inhibitor; and (c) identifying the candidate inhibitor as a MCL-1 or BCL-2 or BCL-X_L inhibitor if the cell viability in step (a) is significantly higher than the cell viability in step (b). The disclosed method provides a way to identify inhibitors which selectively inhibit specific members of the BCL-2 family (e.g., MCL-1) by screening two or more cell lines with addictions to different and specific members of the BCL-2 family of proteins.